It is known that thromboxane A.sub.2 plays a role in ischemic tissue damage. A number of human studies have demonstrated that aspirin, an inhibitor of thromboxane production, decreases the incidence of stroke (cerebral ischemia) and myocardial infarction (myocardial ischemia) in certain patient populations. The role of thromboxane in skin injury is less clear. However, evidence from animal studies suggests that thromboxane A.sub.2 plays an important role in skin injury.
Thromboxane A.sub.2 is present in burned skin (J. P. Heggers, G. L. Loy, M. C. Robson, and E. J. Del Beccaro, Histological Demonstration of Prostaglandins and Thromboxanes in Burned Tissue, Journal of Surgical Research, 28(2):110-117, 1980) and systemically administered imidazole, methyl prednisolone and topical Dermoid Aloe, nonspecific inhibitors of thromboxane production diminish injury following electrical burns (M. C. Robson, R. C. Murphy, and J. P. Heggers. A New Explanation for the Progressive Tissue Loss in Electrical Injuries, Plastic and Reconstructive Surgery, 73(3):431-437, 1984 and J. P. Heggers, M. C. Robson, and L. S. Zachary, Thromboxane Inhibitors for the Prevention of Progressive Dermal Ischemia Due to the Thermal Injury, Burn Care, 6(6):466-468, 1985). Adrenal steroids, indomethacin, aspirin, and methimazole (all nonspecific inhibitors of thromboxane A.sub.2 synthesis) preserve skin blood flow and improve healing following scald burns (M. C. Robson, E. J. Del Beccaro, and J. P. Heggers, The Effect of Prostaglandins on the Dermal Microcirculation After Burning, and the Inhibition of the Effect by Specific Pharmacological Agents Plastic and Reconstructive Surgery, 63(6):781-787, 1979 and E. J. Del Beccaro, M. C. Robson, J. P. Heggers, and R. Swaminathan, The Use of Specific Thromboxane Inhibitors to Preserve the Dermal Microcirculation After Burning, Surgery, 87(2):137-141, 1980). Furthermore, topical administration of imidazole, or UK 38485 or U 63557A (nonspecific inhibitors of thromboxane A.sub.2 synthesis) improved healing following scald burns (J. P. Heggers et al, Burn Care, 6(6):466-468, 1985). In a model of traumatic skin injury, UK 38485 increased tissue survival (L. S. Zachary, J. P. Heggers, M. C. Robson, R. C. Murphy, Combined Prostacyclin and Thromboxane Synthetase Inhibitor UK 38485 in Flap Survival. Annals of Plastic Surgery, 17(2):112-115, 1986).
In addition, the results of in vitro studies suggest that the platelet release reaction (a thromboxane A.sub.2 dependent process) plays a role in the platelet injury associated with dermonecrosis following the bite of the venomous brown recluse spider (R. Rees, J. Hawiger, R. M. Des Prez, and L. E. King, Mechanism of Platelet Injury Associated with Dermonecrosis Resulting from Brown Recluse Spider Venom, Clinical Research 30:265A, 1982).
To date, studies of the role of thromboxane A.sub.2 in skin injury have used inhibitors that are nonspecific, altering the production of multiple substances in addition to thromboxane A.sub.2.